Brainstem serotonergic, catecholaminergic, and inflammatory adaptations during chronic hypercapnia in goats.

Despite the prevalence of CO retention in human disease, little is known about the adaptive neurobiological effects of chronic hypercapnia. We have recently shown 30-d exposure to increased inspired CO (InCO) leads to a steady-state ventilation that exceeds the level predicted by the sustained acidosis and the acute CO/H chemoreflex, suggesting plasticity within respiratory control centers. Based on data showing brainstem changes in aminergic and inflammatory signaling during carotid body denervation-induced hypercapnia, we hypothesized chronic hypercapnia will lead to similar changes. We found that: ) increased InCO increased IL-1β in the medullary raphe (MR), ventral respiratory column, and cuneate nucleus after 24 h, but not after 30 d of hypercapnia; ) the number of serotonergic and total neurons were reduced within the MR and ventrolateral medulla following 30 d of increased InCO; ) markers of tryptophan metabolism were altered following 24 h, but not 30 d of InCO; and ) there were few changes in brainstem amine levels following 24 h or 30 d of increased InCO. We conclude that these changes may contribute to initiating or maintaining respiratory neuroplasticity during chronic hypercapnia but alone do not account for ventilatory acclimatization to chronic increased InCO.-Burgraff, N. J., Neumueller, S. E., Buchholz, K. J., LeClaire, J., Hodges, M. R., Pan, L., Forster, H. V. Brainstem serotonergic, catecholaminergic, and inflammatory adaptations during chronic hypercapnia in goats.